Bovine respiratory disease (BRD) currently accounts for annual losses to the beef cattle industry of about 225 millions of dollars. Considered by major feeder cattle associations and livestock groups as the principal disease problem encountered with beef cattle, the malady represents an estimated death loss amounting to an annual 220 million pounds of carcass beef. The most prevalent of the respiratory diseases is generally known as "Shipping Fever Complex" and is a member of the triumvirate of bovine respiratory diseases (BRD) of feedlot cattle along with Viral Bovine Rhinotracheitis (VBR) and Calf Diptheria. BRD (Shipping Fever Complex) is found to occur in cattle of both sexes, six to twenty-four months of age. The incidence, greatest during late autumn and winter, develops within about ten days of arrival of cattle in feedlots.
While the pathogenesis of shipping fever complex has not been fully elucidated, investigators have deduced three positive factors, to wit, environmental stressing agents, virus and bacteria. Each of these factors separately produces adverse results on cattle, however, their combination is seen to exhibit additive effects. Environmental stresses vary in severity and effect, and the adverse conditions during transit from pasture or range to feedlot have been found to initiate the disease process. Weaning, vehicular vibrations, crowding, cooling and overheating also are noted as being among the physical factors, while fear, anxiety, and noise are deemed psychological factors. A more detailed discourse concerning the pathogenesis of shipping fever complex will be found in the following publication:
I. diseases of Feedlot Cattle, by Jensen et al, Lea & Febiger, 2nd Ed. Philadelphia, Pa. 1971. PA1 Ii. carter, G. R.: Observations on the Pathology and Bacteriology of Shipping Fever in Canada. Canad. J. Comp. Med., 18 (1954): 359-363. PA1 Iii. baldwin, et al, Experimental Infection of Calves with Myxovirus Parainfluenza 3 and Pasteurella Hemolytica. AJVR 28 (1967): pp. 1773-1782 PA1 Iv. gale et al, Studies on Shipping Fever of Cattle. I. Experimental Exposure of Cattle with Various Cultures of Pasteurella. AJVR. 19 (1958): pp. 815-817. PA1 V. collins, F. M. and J. B. Woolcock. Immune responses to Pasteurella multocida in mouse. J. Reticuloendothelial Soc. 19, (1976), 5: 311-321. PA1 Vi. wilkie, B. N., et al, Nonspecific immunosuppression induced in mice with killed Pasteurella hemolytica in Freund's Complete Adjuvant. Int. Archs. Allergy Appl. Immun. 50 (1976): 745-750. PA1 Vii. reisinger, et al, A Myxovirus (SF-4) Associated with Shipping Fever of Cattle, JAVMA. 135 (1959): 147-152. PA1 Viii. heddleston, et al, Studies on the Transmission and Etiology of Bovine Shipping Fever, AJVR, 23 (1969) pp 548-553.
Investigations to the present have indicated that BRD (Shipping Fever Complex) is an interaction of several etiologic agents, Pasteurella hemolytica or Pasteurella multocida, Mycoplasma sp. and respiratory viruses, for instance, Myxovirus, parainfluenza-3(SF-4). These agents have been isolated singly and in combination from beef calves during outbreaks of BRD.
At the outset of the investigations, bacteriological and pathological studies resulted in the consistent isolation of P. hemolytica and/or P. multocida from diseased lungs. See for example the following publication:
When freshly isolated cultures of P. hemolytica and P. multocida were innoculated into healthy cattle, only variable results have been obtained, when the organisms in aerosol were administered into the nose, a mild febril reaction has been produced and essentially no reaction has been observed when similar orgnisims are injected subcutaneously. In this regard, see the following publications:
Investigations seeking an immunoresponse to BRD through the use of Pasteurella bacterins have shown that, while high levels of serum antibody may be evoked, the animals tested generally were not protected against infection. It has been reported that mice vaccinated by the subcutaneous route were fully protected against parenteral challenge but only partially protected against aerogenic infection by P. multocida. See, for example:
Further, it has been shown that a single injection of P. hemolytica bacterin with Freund's adjuvant is, in fact, immunosuppressive to the antigens of sheep red blood cells. See:
The historical development of the research into bacterial pathogens as the cause of BRD led investigators to postulate that the primary cause was a viral agent. The initial isolation of such a virus occured in 1959 leading to the classification of the above identified myxovirus parainfluenza-3 (SF-4). See in this regard:
When innoculated intranasally as an aerosol into healthy young cattle, the newly isolated virus usually caused a febrile reaction for about six days, but did not cause the entire antipical syndrome of BRD. (See publication VII above). However, the exposure of healthy cattle in close sequence to both myxovirus parainfluenza-3 (SF-4) and P. hemolytica or P. multocida caused more severe disease than virus alone, however the entire syndrome of Shipping Fever Complex has been described as not being reproduced, it being opined that the inclusion of a third positive factor, the above-noted appropriate environmental stress, may have been the requirement for full manifestation of the disease. See:
Following the noted isolation of viral agents, studies of the efficacy of an appropriate vaccine have been somewhat concentrated along the conventional techniques of using a modified live virus to stimulate the in vivo production of antibodies. The results of these efforts, however, have not been definitive (See publication I supra.). Some vaccines have been developed containing variable combinations of antigens from viral agents and bacterins, for instance, as described in U.S. Pat. No. 3,634,587. However, their efficacy is described as requiring further clarification (Publication I supra). At the present time all known immunizing agents appear to contain different combinations of attenuated live virus, inactivated virus and killed pasteurella sp., the latter being commonly referred to as "bacterins". Intranasal administration has been described as stimulating the formation of nasal secretion antibodies and may be more effective than parenteral innoculation (Publication I, supra).
The treatment of the disease once developed generally involves the administration of antibiotics as well as electrolytes and arsenical compounds in drinking water. However, at the present time, many feeder calf operations are experiencing an increased mortality in newly shipped cattle due to the emergence of strains of Pasteurella bacteria that are resistant to all antibiotics and chemotherapeutic drugs which are presently approved for a treatment of food-producing animals. These resistant strains have been isolated from several midwestern states and California. When outbreaks of BRD-SFC occured in groups of calves in which the resistant strains were present, morbidity has been as great as 90% and mortality has ranged from 10-20%. The widespread evolution of these drug-resistant strains of Pasteurella sp. indicates an important need for the development of an effective and practical vaccination procedure.